The virtual 2020 Global Drug Bioavailability Enhancement Summit this past December showcased novel technologies and platforms aimed at addressing bioavailability and solubility challenges. These included techniques like electrospinning, mesoporous silica technology, physiochemical optimization, amorphous nanoparticle engineering, and pharmacokinetic modeling. And the end goal is the same: Save time and money while accelerating formulation development.
Proprietary Technologies for Amphiphilic Molecules
Some biologics require high concentrations to be effective, even though they may be soluble. Formulating at these high concentrations can lead to issues with solubility or viscosity, requiring advanced delivery technologies such as the formulation of nanoparticles or microparticles. These engineered particles flow well even at high concentrations.
Formulation strategy is determined by looking at the physicochemical characteristics of a given active pharmaceutical ingredient (API). For crystalline API compounds with high melting points, a go-to technology for Lubrizol Life Science Health (LLS Health) is nanomilling, which reduces the size and increases the dissolution rate.
“Depending on lipid solubility, nanoemulsions or our proprietary LyoCell® technology can be useful approaches,” says Dr. Robert Lee, President, LLS Health, CDMO Division. “LyoCells are better able to accommodate amphiphilic molecules (i.e., those with both a hydrophilic and a hydrophobic region) and are compatible with both small molecules and biologics.”
Assessing the feasibility of nanomilling provides clients with a cost-effective and efficient way to determine whether particle size reduction will work for their API, he continues. Nanomilling is well suited for formulating APIs with poor aqueous solubility and has been used in a range of dosage forms, including liquids, capsules, tablets, and injectables. “Because this process is in an aqueous vehicle, it bypasses the problems associated with the large volumes and flammability of organic solvents used in other methods; it is also scalable and commercially validated,” he says.
Nanomilled API particles — nanoparticles — can be formulated as liquids, lyophilized powders, or oral solid dosage forms. Solid-lipid nanoparticles (SLNs) are submicron lipid particles that are used as an API delivery vehicle, including for hydrophobic and high molecular weight APIs. “Their cost and recognized safety make them an attractive alternative,” says Dr. Lee.
Polymeric nanoparticles are a relatively new addition to the solubility arsenal and have been used with serum albumin to make such drugs as Abraxane®. Additionally, other particulate systems comprised of inorganic compounds — silica, magnetite, gold — in a formulation matrix or coating that incorporates chemotherapeutics or other APIs can improve bioavailability.
LLS Health has also developed SATx technology, an interpretation of antibody-drug conjugates in which the surface of a nanoparticle loaded with a chemotherapeutic agent is decorated with biologics or targeting molecules, such as monoclonal antibodies. The SATx technology has been successfully applied to vaccines, says Dr. Lee.”